Alzheimer's disease is a disease characterized by senile plaques, β-amyloid deposits, and neurofibrillary tangles in the cerebral cortex and subcortical gray matter. Its main symptom is progressive cognitive deterioration (hereinafter “dementia”) and, in addition to this symptom, depression, schizophrenia-like symptoms (such as delusions and hallucinations), agitation, aggressive behaviors, and so-called apathy, which is an enervation-like symptom, are also known to occur (Schatzberg et al., “Seishin Shinkei Yakurigagu Daijiten,” Nishimura Shoten, 2009, p. 785). The incidence rate of Alzheimer's disease is increased with age, and it is said that, in people aged 85 years or older, the rate reaches as high as 40% or more. Therefore, in aging societies such as Japan, it is an urgent task to develop a therapeutic agent for Alzheimer's disease.
At present, donepezil, rivastigmine, galantamine and tacrine, which are inhibitors of cholinesterase, an acetylcholine-degrading enzyme, have been used as a therapeutic agent or a prophylactic agent for dementia caused by Alzheimer's disease. In addition, memantine, which is an N-methyl-D-aspartate (hereinafter “NMDA”) receptor antagonist, has been used in Europe and the U.S. (Miller et al., Geriatr Nurs, 2004, Vol. 25, p. 56).
Some of the existing therapeutic agents for Alzheimer's disease have been reported to have an analgesic effect on neuropathic pain. For example, it has been reported that donepezil exhibits an analgesic effect on a rat neuropathic pain model (Clayton et al., Anesthesiology, 2007, Vol. 106, p. 1010). In addition, it has been reported that memantine exhibits an analgesic effect on a rat diabetic neuropathic pain model (Chen et al., Neuropharmacoogy, 2009, Vol. 57, p. 121) and also exhibits an analgesic effect on patients with complex regional pain syndrome which is one of neuropathic pains (Sinia et al., Clin J Pain, 2007, Vol. 23, p. 273).
On the other hand, although there are reports suggesting that a pyrazole derivative of the following Formula which is characterized by having the sulfonyl group on the aromatic ring (WO 00/066562) and a pyrazole derivative which acts on estrogen receptors (WO 00/007996) are effective in treating Alzheimer's disease, such effectiveness of a cyclohexane derivative is not disclosed nor suggest at all.

In addition, although a pyrazole derivative that is effective as an analgesic or a therapeutic agent for neuropathic pain has been known (WO 08/105,383), there are no reports about its therapeutic effect on Alzheimer's disease.
However, there is concern that cholinesterase inhibitors, which are the existing therapeutic agents for Alzheimer's disease, may produce side effects on autonomically innervated organs such as heart and intestine and, therefore, the dose thereof is restricted (Schatzberg et al. eds., “Seishin Shinkei Yakurigagu Daijiten,” Nishimura Shoten, 2009, p. 669). Hence, a sufficient therapeutic effect against Alzheimer's disease cannot be obtained and, moreover, the therapeutic effect tends to be reduced if they are used continually.
Accordingly, it could be helpful to provide a therapeutic agent and a prophylactic agent for Alzheimer's disease which have an effect to inhibit or delay the progress of Alzheimer's disease and whose therapeutic effect against Alzheimer's disease last for a long time even when used for a long period of time.